Trial Description

To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC

To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD-L1- High UC

Secondary Outcome:

To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS in patients with PD-L1-High UC

To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS in patients with UC

To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR

To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR

To assess disease-related symptoms and HRQoL in UC patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared with SoC and each other using the FACT-BL questionnaire

To assess the serum concentration of MEDI4736/tremelimumab of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy

To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy

To assess the objective response rate (ORR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible

To assess the duration of response (DoR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible

This is a randomized, open-label, controlled, multi-centre, global Phase III study to
determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy and MEDI4736
(Durvalumab) in combination with tremelimumab versus SoC (cisplatin + gemcitabine or
carboplatin + gemcitabine doublet) first-line chemotherapy in treatment-naïve patients with
histologically or cytologically documented, unresectable, Stage IV transitional cell
carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the
urothelium (including renal pelvis, ureters, urinary bladder, and urethra) and to allow
sufficient flexibility for Investigators and patients to select the agents that reflect their
normal clinical practice and national guidelines. The patients enrolled in the study will be
randomized 1:1:1 to receive treatment with combination therapy, monotherapy, or SoC
(cisplatin + gemcitabine or carboplatin + gemcitabine, based on cisplatin eligibility).
Patients will be treated with MEDI4736 (Durvalumab) or MEDI4736 (Durvalumab) with
tremelimumab, or treated with SoC until progressive disease (PD) is confirmed, unacceptable
toxicity occurs, withdrawal of consent, or another discontinuation criterion is met. Patients
will be followed for up to 2 years.